Chronic and Acute Intranasal Oxytocin Produce Divergent Social Effects in Mice

Abstract

Intranasal administration of oxytocin (OXT) might be a promising new adjunctive therapy for mental disorders characterized by social behavioral alterations such as autism and schizophrenia. Despite promising initial studies in humans, it is not yet clear the specificity of the behavioral effects induced by chronic intranasal OXT and if chronic intranasal OXT could have different effects compared with single administration. This is critical for the aforementioned chronic mental disorders that might potentially involve life-long treatments. As a first step to address these issues, here we report that chronic intranasal OXT treatment in wild-type C57BL/6J adult mice produced a selective reduction of social behaviors concomitant to a reduction of the OXT receptors throughout the brain. Conversely, acute intranasal OXT treatment produced partial increases in social behaviors towards opposite-sex novel-stimulus female mice, while on the other hand, it decreased social exploration of same-sex novel stimulus male mice, without affecting social behavior towards familiar stimulus male mice. Finally, prolonged exposure to intranasal OXT treatments did not alter, in wild-type animals, parameters of general health such as body weight, locomotor activity, olfactory and auditory functions, nor parameters of memory and sensorimotor gating abilities. These results indicate that a prolonged over-stimulation of a 'healthy' oxytocinergic brain system, with no inherent deficits in social interaction and normal endogenous levels of OXT, results in specific detrimental effects in social behaviors.

Brain Oxytocin in Social Fear Conditioning and Its Extinction: Involvement of the Lateral Septum

“…While our data implicate OXT as a treatment option for disorders associated with social fear, such as SAD, more detailed studies regarding acute and long-term treatment effects on molecular, neuronal, and behavioral levels are required. This is more evident as chronic central as well as peripheral OXT treatment in mice affected brain OXTR binding (Huang et al, 2013;Peters et al, 2014).…”

Developmental Perspectives on Oxytocin and Vasopressin

“…These data highlight important timing (acute vs chronic and developing vs mature), dose, and sex effects on social behavior outcomes after exogenous manipulation of oxytocin. A recent study in adult male mice also revealed a counterintuitive reduction in social investigation after chronic intranasal oxytocin (Huang et al, 2014). Combined, these data indicate caution and careful study design for future chronic use of oxytocin in clinical populations.…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…injection of high OT doses in mice produced higher anxiety-like behavior in a social stress paradigm, which was paralleled by reductions in OTR binding in various brain areas (e.g., amygdala, septum) relevant for stress-regulation (Peters et al, 2014). Similarly, chronic intranasal OT treatment resulted in a reduction of social behaviors and concurrent reductions of OTR binding in the nAcc, amygdala, and anterior olfactory nucleus amongst other brain regions (Huang et al, 2014). Moreover, in a mouse model of ASD, chronic intranasal OT administration did not lead to improvements in social behaviors (Bales et al, 2014).…”